Provide cold-adapted reassortant vaccines of influenza virus types A and B with the relevant surface antigens for use inman. Identify a stable, high yielding donor strain for use in producing type B reassortant vaccines. Derive and characterize reassortants of both type A and B ca donor viruses with single genes from these ca patients. Test isolatesfrom field vaccine trials for anomalies in biological markers and subsequently in genotypes. Provide and sequence recombinant DNA clones of both types A and B donor genes. Furnish baseline data from the use of bivalent and polyvalentca vaccine preparations in an animal model for application in man. The approaches are designed to establish the geneticmechanisms of cold adaptation and attenuation. The efforts necessary to achieve these objectives will be performed withcost effectiveness along guidelines for the eventual licensing of these vaccines.